This project was designed to evaluate the neurochemical basis of seizure phononena. Studies will be conducted exclusively in the hippocampal formation of the rat since this brain area is known to be one of the most epileptogenic regions throughout the brain. Intrahippocampal injections of the convulsant kainic acid, which also mimic the severe neuronal loss observed in human epileptic tissue, will be employed for studying morphological and neurochemical concomitants of hippocampal seizures. The effects of kainic acid will be compared with those of bicuculline, a convulsant which may act via a different cellular mechanism. Particular emphasis will be placed on the involvement of three putative neurotransmitter systems thought to play important roles in the initiation and/or propagation of seizure phenomena: glutamic acid, GABA and norepinephrine. Lesions of hippocampal intrinsic neurons and afferents and in vitro receptor-binding and release studies will be used in combination with the convulsants to learn more about the neurochemical circuitry associated with convulsive disorders. Finally, the interaction between five chemical classes of anticonvulsant drugs and glutamate, GABA and norepinephrine, respectively, will be evaluated under a variety of experimental conditions. This study should therefore yield relevant new information on chemical parameters which are significantly involved in pathogenesis, neuropathology and therapy of temporal lobe epilepsy.